Reduced microvascular endothelial function in young female e-cigarette users is not driven by reduced chronic estradiol exposure

Kelsey Schwartz; Elizabeth Wetzel; Claire Goebel; Josalyn Cho; Anna Stanhewicz

doi:10.1152/physiol.2026.41.S1.2293163

Abstract only Chronic electronic cigarette (EC) use is associated with reduced vascular endothelial function in otherwise healthy young EC users, and emerging evidence suggests that female EC users may have greater reductions in endothelial function compared to males. Chronic tobacco cigarette smoking is a greater predictor of cardiovascular disease (CVD) morbidity in females than in males, which may be mediated, in part, by reduced estradiol (E2) exposure across the menstrual cycle. Whether similar decreases in E2 exposure are present and contribute to reduced endothelial function in female EC users is unexplored. We hypothesized that 1) endothelial function would be reduced to a greater extent in EC females compared to EC males, and 2) E2 exposure across the menstrual cycle would be lower in female EC compared to female healthy controls (HC) and would be inversely related to endothelium- and nitric oxide (NO)-dependent dilation. 20 HC (21±2 yrs; 10M/10F) and 12 EC (20±2 yrs; 6M/6F) had one intradermal microdialysis fiber placed in the ventral forearm and underwent a standard local heating (LH) protocol (42°C; 0.1°C·s-1) to assess endothelium-dependent dilation. After full expression of the LH response, 15mM L-NAME (NO-synthase inhibitor) was perfused to assess NO-dependent dilation. Red cell flux was measured over the site with laser-Doppler flowmetry. Cutaneous vascular conductance was calculated (CVC=flux/mean arterial pressure) and normalized to maximum (%CVCmax; 28mM SNP+43°C). Female participants collected daily first morning urine samples for 1 menstrual cycle (29±6 days) before the study visit. Urine E2 was measured via ELISA, expressed relative to creatinine (pg/mg cre/mL), and individual area under the curve was calculated for E2 exposure (pg/mg cre/mL/day). Pearson correlations were used to evaluate the relation between microvascular function and E2 exposure. Between groups, EC users had attenuated endothelium- (EC: 77±10 vs HC: 88±6%CVCmax; p< 0.001) and NO-dependent (EC: 59±11 vs HC: 70±10%; p=0.002) dilation responses to LH. Within female sex, EC had lower endothelium- (EC: 77±7 vs HC: 90±6%; p< 0.001) and NO-dependent (EC: 59±10 vs HC: 74±11%; p=0.003) dilation compared to HC. There were no group differences within male sex (both p>0.05). Within females, E2 exposure was greater in EC users compared to HC (1896±740 vs 1102±408 pg/mg cre/mL/day; p=0.007). E2 exposure was not related to endothelium- or NO-dependent dilation in females in either group (all p>0.05). These data demonstrate that otherwise healthy young EC users have reduced microvascular endothelium- and NO-dependent dilation compared to non-users, and these responses are driven by greater reductions in females. Contrary to our hypothesis, E2 exposure was greater in female EC users compared to female HC, suggesting that other physiological mechanisms may underlie sex differences in endothelial dysfunction in young EC users. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Reduced microvascular endothelial function in young female e-cigarette users is not driven by reduced chronic estradiol exposure

View Online

Abstract

Details

Metrics